There is an urgent need to develop and test alternate, more effective and less expensive interdictions for HIV-1 infection and AIDS. We propose to do so by developing an improved delivery vehicle for HIV-1 vaccines by utilizing polymeric nanospheres to protect and sustain the release of viral glycoproteins. This drug delivery vehicle will have the capability to deliver either a whole inactivated HIV-1 vaccine and1or HIV-1 subunit vaccines. We plan to nanoencapsulate HIV-1 antigens by utilizing an extremely effective nanoencapsulation technique, which utilizes supercritical and near-critical fluids w/wo polar cosolvents (SuperFluids(TM)) Use of SuperFluids(TM) to replace potentially harmful organic solvents, such as methylene chloride, will eliminate the adverse effect of organic solvent to the potent but sensitive antigens, reduce cost by eliminating unnecessary processing steps, and improve the manufacturing environment. In conjunction with the potential ability of the SuperFluids(TM) process to inactivate live virus particles yet maintain antigenicity, this technique would also allow for the nanoencapsulation of safe AIDS vaccines intact HIV-1 virions. Cocktail mixtures of different HIV-1 strains could also be nanoencapsulated to generate broad-based immunity. The HIV-1 vaccine nanoencapsulation technology that we propose is quite inexpensive, amenable to large-scale processing, and quite portable. PROPOSED COMMERCIAL APPLICATIONS The development of a safe, effective, and economical HIV therapeutic vaccine will be of tremendous value to the approximately 23 million people infected with HIV, and to the public health of the United States and the world.